Duration of antibiotic therapy for ventilator-associated pneumonia caused by non-fermentative gram-negative bacilli

BACKGROUND AND PURPOSE: Chastre et al. compared eight and 15 days of antibiotic therapy for ventilator-associated pneumonia (VAP), finding no difference in outcome with the exception of VAP caused by non-fermentative gram-negative bacilli (NFGNB), for which a higher recurrence rate was seen in the shorter-duration group (JAMA 2003;290:2588-2598). We recently examined our institutional experience with VAP caused by NFGNB to determine whether shorter courses of antibiotic therapy were associated with higher rates of recurrence. METHODS: Data collected on all patients completing treatment for VAP in a surgical/trauma intensive care unit from December 1996 to October 2004 were analyzed retrospectively for the relations between the duration of antibiotic therapy and recurrence and in-hospital mortality rates. RESULTS: Of the 452 episodes of VAP, 154 were associated with NFGNB. Twenty-seven patients were treated with 3-8 days (mean 6.4 +/- 0.3 days) of antibiotics, whereas 127 received nine or more days (mean 17.1 +/- 0.7 days) of therapy. The recurrence rate for infections treated with the shorter course was 22% vs. 34% for patients receiving nine or more days of antibiotics (p = 0.27). The mortality rates were 22% and 14%, respectively (p = 0.38). Similar trends were demonstrated for infections caused by other organisms. CONCLUSIONS: We did not find a higher recurrence rate in patients with VAP caused by NFGNB who received shorter courses of antibiotic therapy. On the contrary, those patients receiving shorter courses trended toward lower rates of recurrence. Pending further prospective trials addressing the duration of antibiotic treatment for patients with VAP caused by NFGNB, shorter courses of treatment, perhaps based on improvement in clinical parameters, may be warranted.     

Alternaria alternata soft tissue infection in a forearm transplant recipient

BACKGROUND: Composite tissue allograft recipients require intensive immunosuppression and are therefore at risk of infections. Filamentous fungal infections are among the complications most difficult to manage in organ transplant recipients. METHODS: Case report and literature review. CASE REPORT: Two years after bilateral forearm transplantation, a 35-year-old patient presented with a tumor-like lesion on his thigh after a penetrating injury caused by a sliver acquired during hiking. The lesion was excised completely, and microscopic examination revealed a filamentous fungal infection. Alternaria alternata was identified as the causative agent. Induction therapy with liposomal amphotericin B for one week followed by oral itraconazole maintenance therapy for eight weeks was successful, with no signs of recurrence or side effects at 18 months' follow-up. CONCLUSION: This is the first reported case of invasive A. alternata infection in a composite tissue allograft recipient. The infection was managed successfully with local excision and systemic antifungal treatment.     

Single-institutional experience with the surgical infection prevention project in intra-abdominal surgery

BACKGROUND: The incidence of surgical site infection (SSI) is becoming a key component of standard measures of quality of performance. We hypothesized that institutional implementation of a protocol targeting known risk factors would reduce the incidence of SSI associated with intra-abdominal surgery. METHODS: Beginning in June 2004, a quality control initiative was implemented to prevent SSI in patients undergoing intra-abdominal surgical procedures at an academic medical center. This protocol included administration of the proper prophylactic antibiotic 0-60 minutes before incision, continued antibiotic administration for or=36 degrees C), along with good glycemic control (goal<200 mg/dL 48 h postoperatively) in diabetic patients. Baseline data collected during the initial four months of protocol development (379 patients) were compared with data collected during the last four months of the 11-month study period (390 patients). RESULTS: Compliance with antibiotic selection increased from 89 percent to 97 percent (p 相似文献   

ELISA assays and alcohol: increasing carbon chain length can interfere with detection of cytokines

Enzyme-linked immunosorbent assays (ELISAs) are frequently used in studies on cytokine production in response to treatment of cell cultures or laboratory animals. When an ELISA assay is performed on cell culture supernatants, samples often contain the treatment agents. The purpose of the present study was to determine if some of the agents evaluated might inhibit cytokine detection by interfering with the ELISA, leaving the question of whether cytokine production was inhibited unanswered. Mouse and human cytokine ELISA kits from BD Biosciences were used according to the manufacturer’s instructions. Cytokine proteins were subjected to one to five carbon alcohols at 86.8 mM (methanol, ethanol, 1-propanol, 2-propanol, n-butanol, and n-pentanol). After treating cell cultures with alcohols of different carbon chain lengths, we found that some of the alcohols interfered with measurement of some cytokines by ELISA, thus making their effects on cytokine production by cells in culture unclear. Increasing carbon chain length of straight chain alcohols positively correlated with their ability to inhibit detection of tumor necrosis factor alpha (TNF-α) and interleukin 10 (IL-10), but not with the detection of interleukin 6 (IL-6), interleukin 8, (IL-8), and interleukin 12 (IL-12). To avoid misinterpretation of treatment effects, ELISA assays should be tested with the reference protein and the treatment agent first, before testing biological samples. These results along with other recent results we obtained using circular dichroism indicate that alcohols with two or more carbons can directly alter protein conformation enough to disrupt binding in an ELISA (shown in the present study) or to inhibit ligand-induced conformational changes (results not shown). Such direct effects have not been given enough consideration as a mechanism of ethanol action in the immune system.     

Quantitative Analysis of the Neuroendocrine–Immune Axis: Linear Modeling of the Effects of Exogenous Corticosterone and Restraint Stress on Lymphocyte Subpopulations in the Spleen and Thymus in Female B6C3F1 Mice

The effects of exogenous corticosterone and restraint stress on the number and percentage of lymphocyte subpopulations in the spleen and thymus were evaluated. The data were used to generate linear models that describe the relationship between these parameters and the area under the corticosterone concentration vs time curve (AUC). Comparison of the models revealed that the number of nucleated cells in the spleen was decreased similarly by exogenous corticosterone and restraint (at equivalent corticosterone AUC values). However, exogenous corticosterone caused a greater decrease in cell number in the thymus than it did in the spleen. Corticosterone preferentially depleted CD4⁺CD8⁺ cells in the thymus, whereas the same corticosterone exposure produced by restraint stress did not. In the spleen, cell number for all major cell types was decreased by both treatments, but there were minor differences in the change in percentage of some subpopulations induced by exogenous corticosterone as compared to restraint. The models derived here provide quantitative data that indicate the magnitude of corticosterone and stress-induced effects on lymphocyte populations in the spleen and thymus. These results have mechanistic implications, and they may be useful in future efforts to extrapolate from mouse to human by completing a risk assessment parallelogram.     

PCV16 Smoking Related Costs in the United States

Smoking is a high-risk behavior that affects the health and economic welfare of society. Thus, it is important to quantify the economic burden smoking places on social institutions in the United States.
OBJECTIVE: The purpose of this review paper is to analyze smoking cost studies and to provide estimates that represent the economic costs of smoking from different perspectives of society, and as a whole.
METHODS: Current Contents (1996–), Health Star (1970–), and Medline (1966–) databases were searched through the use of pertinent subject headings and key words: tobacco use, smoking, cost, and economics. The internet was utilized to identify potential sources of epidemiological and cost information on smoking. Recent cost-of-illness studies using different methodologies: human capital, incidence, and prevalence were chosen for review based on their relevance.
RESULTS: Preliminary results indicate that the published cost studies available underestimate the "true" costs of smoking. The most current articles approximate annual direct medical costs to health care payers of $50 billion (1993); inflating to 1997 equals $59 billion or $1,200 per smoker. Although the latest cost studies do not attempt to estimate indirect costs, past studies have found indirect costs to be 1.5–2 times the direct costs. Therefore, using direct and indirect costs we estimate total smoking costs to be $150 billion (1993); inflating to 1997 equals $176 billion or $3,500 per smoker.
CONCLUSION: Quantifying the cost of smoking is a difficult task due to tobacco use infiltrating many aspects of life and the dependency of cost on perspective. Cost-of-illness studies provide cost estimation data which can be useful in aiding decision-makers who are allocating health care resources.     

Differences in IL-10 and IL-12 production patterns and differences in the effects of acute ethanol treatment on macrophages in vivo and in vitro.

Several recent studies have documented that signaling can be fundamentally different in vivo and in vitro. However, studies of signaling and cytokine production by macrophages are often conducted in vitro, without confirmation in vivo. In addition, the direct effects of drugs and chemicals, including ethanol, on these processes are also often investigated in vitro. The purpose of the present study was to compare production of interleukin-6 (IL-6), IL-10, and IL-12 by macrophages in response to two different ligands for toll-like receptors and the effects of acute ethanol exposure on these responses in vivo and in vitro. The macrophage-like cell line RAW 264.7 is also widely used in cytokine and signaling studies, so these cells were also evaluated in this study. The results indicate that IL-6 production and the effects of Ethanol on IL-6 were similar in vivo and in vitro. In contrast, IL-10 was produced to a much greater extent in vitro than in vivo, and IL-12 was often undetectable in vitro even though it was produced at greater concentrations than IL-10 in vivo. To determine the role of altered secretion of preformed IL-10 as compared to new synthesis, cells were treated in vitro with protein and mRNA synthesis inhibitors. The results suggest that preformed IL-10 is released in vivo, but almost all IL-10 secreted in vitro is newly synthesized. Ethanol suppressed IL-12 and enhanced or had no effect on IL-10 production in vivo, whereas it decreased IL-10 production in vitro. These effects were similar at different times and using different concentrations of toll-like receptor ligands. In general, RAW 264.7 cells responded similarly to peritoneal macrophages in vitro. This suggests that results for cytokine studies and probably signaling studies as well that are conducted in vitro should be interpreted with caution and confirmed in vivo, particularly if they involve IL-10 and IL-12.     

Characterization of the p67phox gene: genomic organization and restriction fragment length polymorphism analysis for prenatal diagnosis in chronic granulomatous disease

The genetic defect in the p67phox-deficient form of chronic granulomatous disease (CGD) follows an autosomal recessive pattern of inheritance. When genomic DNA from normal individuals is digested with HindIII and probed with p67phox cDNA an allelic restriction fragment length polymorphism (RFLP) of 4.0 kb or 2.3 kb is detected. We cloned and characterized the p67phox gene using the cDNA and sequenced the exon/intron boundaries, mapping 16 exons on the 40-kb gene. The polymorphic region was then sequenced to identify the inheritance pattern of amniocentesis-derived fetal cells by genomic amplification. The proband, a 9-year-old female patient with p67phox-deficient CGD, and her phenotypically normal mother are homozygous for the RFLP marker, whereas the father and two brothers are heterozygous. The fetus was shown to be heterozygous as well, showing it had inherited at least one normal p67phox gene from the father and that it was predicted to have a normal phenotype. Cord blood samples at birth showed normal oxidative function. Amplification allows rapid detection of the inheritance pattern for fetal diagnosis in informative families. We report the genomic structure of p67phox and an amplification-based method for detection of the marker on chromosome 1q25, used here for prenatal diagnosis of CGD.     

Improved specificity and sensitivity when using pronase-digested lymphocytes to perform flow-cytometric crossmatch prior to renal transplantation

Several laboratories have resorted to flow-cytometric crossmatch (FCXM) in an effort to prevent hyperacute and accelerated renal allograft rejections. The currently employed FCXM has problems with both false-positive and -negative reactions, largely as a result of irrelevant IgG binding to Fc IgG receptors. In 1980, we circumvented this problem by digesting Fc IgG receptors with pronase, and demonstrated that, with immunofluorescence microscopy (IF), detection of IgG anti-HLA antibodies was highly sensitive and specific. In 1995, we introduced the pronase technique to FCXM and showed that this enzyme did not decrease HLA expression. We present herein a prospective study at our institution to determine whether FCXM using pronase-digested (PD) lymphocytes is as sensitive and more specific than FCXM with undigested (UD) lymphocytes when compared with the highly sensitive and specific IF assay. In analyzing the 186 donor-specific pre-renal-transplant crossmatches, we found that PD FCXM was as sensitive and specific as IF and was able to detect weak IgG anti-HLA antibodies that bound to B cells. Fourteen of these patients would have been denied transplants if one were to have relied on UD FCXM. The data clearly indicate that PD FCXM can reliably be used to detect weak IgG anti-HLA antibodies before renal transplantation.